Tamoxifen is being given as adjuvant therapy for breast cancer to greater numbers of women and for longer durations. Further, this hormone is under consideration as a chemosuppressive agent. To date, animal data have shown that tamoxifen acts as an antiresorptive agent and preserves bone, but published human studies have not demonstrated definitively this favorable effect. While tamoxifen appears to lower blood cholesterol levels, its impact on high density lipoprotein (HDL) cholesterol is uncertain. The Wisconsin Tamoxifen Study (WTS) (for an extension of which this is a proposal) was a randomized placebo-controlled 2-year toxicity study of tamoxifen 10 mg bid in 140 postmenopausal women with axillary node-negative breast cancer. In the WTS, after 2-years the rate of change in lumbar spine bone mineral density (BMD) was significantly different and preserved in tamoxifen-treated subjects (tamoxifen-treated women +0.61%/year; placebo-treated women -- -0.99%/year HDL lipoprotein cholesterol was minimally depressed by tamoxifen at early measurement times, but not at 18 and 24 months. The current proposal is to examine lumbar spine bone mineral density using dual photon absorptiometry, lipoproteins, and several other critical parameters, once, at 4-5 years from entry, in 2 groups of the WTS study participants available to study: 1) The 32 women (of 70) originally, randomized to tamoxifen treatment who continued this treatment for 4 years; and 2) 42 women (of 70) originally randomized to placebo treatment who continued not taking tamoxifen for 4 years. Analysis comparing BMD in these groups at baseline of the WTS and after 4 years will provide further refined data on the bone effects of tamoxifen which will allow more accurate prediction of its likely long term impact on fracture rates. The cholesterol HDL lipoprotein data will provide information on the long term impact of tamoxifen on heart disease endpoints.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
2R01CA050243-03
Application #
3194632
Study Section
Experimental Therapeutics Subcommittee 1 (ET)
Project Start
1989-09-29
Project End
1993-08-31
Budget Start
1992-09-01
Budget End
1993-08-31
Support Year
3
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of Wisconsin Madison
Department
Type
Schools of Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Cameron, Linda D; Leventhal, Howard; Love, Richard R et al. (2002) Trait anxiety and tamoxifen effects on bone mineral density and sex hormone- binding globulin. Psychosom Med 64:612-20
Love, R R; Anker, G; Yang, Y et al. (1999) Serum homocysteine levels in postmenopausal breast cancer patients treated with tamoxifen. Cancer Lett 145:73-7
Love, R R (1995) Clinical review 70: Approaches to the prevention of breast cancer. J Clin Endocrinol Metab 80:1757-60
Mamby, C C; Love, R R; Lee, K E (1995) Thyroid function test changes with adjuvant tamoxifen therapy in postmenopausal women with breast cancer. J Clin Oncol 13:854-7
Love, R R (1994) Prevention of breast cancer in premenopausal women. J Natl Cancer Inst Monogr :61-5
Mamby, C C; Love, R R; Feyzi, J M (1994) Protein S and protein C level changes with adjuvant tamoxifen therapy in postmenopausal women. Breast Cancer Res Treat 30:311-4
Love, R R; Barden, H S; Mazess, R B et al. (1994) Effect of tamoxifen on lumbar spine bone mineral density in postmenopausal women after 5 years. Arch Intern Med 154:2585-8
Love, R R; Wiebe, D A; Feyzi, J M et al. (1994) Effects of tamoxifen on cardiovascular risk factors in postmenopausal women after 5 years of treatment. J Natl Cancer Inst 86:1534-9
Love, R R (1993) The National Surgical Adjuvant Breast Project (NSABP) Breast Cancer Prevention Trial revisited. Cancer Epidemiol Biomarkers Prev 2:403-7
Love, R R; Surawicz, T S; Williams, E C (1992) Antithrombin III level, fibrinogen level, and platelet count changes with adjuvant tamoxifen therapy. Arch Intern Med 152:317-20

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